Antidiabetic Drugs After the University Group Diabetes Program (UGDP)

Karam, John H.; Matin, Somaieh; Forsham, Peter H.

doi:10.1146/annurev.pa.15.040175.002031

Cited by 21 publications

(14 citation statements)

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“…This complication is linked to their mechanism of action; decreased gluconeogenesis from alanine, pyruvate and lactate [1,8,10] may result in a rise in blood lactate concentration [3,11,12]. Therefore, treatment with biguanides always requires caution.…”

Section: Discussionmentioning

confidence: 99%

Metformin-associated lactic acidosis in Sweden 1977–1991

Wiholm

Myrhed

1993

Eur J Clin Pharmacol

119

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Since the withdrawal of phenformin in 1978, the use of metformin has increased from 13,500 to 22,000 patient years/year. During the period 1977-91 a total of 18 cases of metformin-associated acidosis was reported, of which 16 had lactic acidosis. The incidence of reported acidosis and lactic acidosis decreased from 1.50 cases per 10,000 patient years in 1977-81 to 0.24 cases per 10,000 patient years 1987-91, probably due to lower doses doses and reduced usage in the very old. All the reports described patients with several other concomitant diseases, mainly cardiovascular and renal, when the acidosis was diagnosed. It is important continuously to re-evaluate metformin therapy and to stop treatment at the onset of impaired renal or cardiovascular function.

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Section: Discussionmentioning

confidence: 99%

Metformin-associated lactic acidosis in Sweden 1977–1991

Wiholm

Myrhed

1993

Eur J Clin Pharmacol

119

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“…Phenformin, in contrast, is metabolized by the liver and binds to serum proteins. The mean plasma half-life of phenformin (7.5-15 h) is much longer than that of metformin (14,17).…”

Section: Chemistry and Pharmacodynamics Of Biguanidesmentioning

confidence: 94%

“…They lower the elevated blood glucose levels in patients with NIDDM but do not lower the blood glucose values in nondiabetics unless there has been prolonged fasting (14,15,17). Biguanides, unlike the sulfonylureas, do not stimulate the release of insulin from the p-cells; in fact, biguanide treatment may result in lowered insulin levels (17). The major effects of biguanides are to either potentiate or mimic the actions of insulin (14,(17)(18)(19)(20).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Role of metformin in treatment of diabetes mellitus

Vigneri

Goldfine

1987

Diabetes Care

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Metformin, a biguanide antidiabetic agent that can be administered either alone or in combination with sulfonylureas, has been extensively used in Europe and Canada. The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action. Metformin, because of its chemical structure, does not interact with the liver and has a short half-life. Consequently, lactic acidosis, which is a rare complication of metformin, has not been associated with the proper use of this drug. In addition to its antidiabetic actions, metformin causes weight loss in obese diabetic patients and may be useful in managing associated lipid disorders.

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“…The University Group Diabetic Program, the best known attempt to measure them, gave the 'wrong' answer, and has been extensively criticised (e.g. Fuller 1983;Karam et al 1975). Comparative studies are hampered by lack of data on the relative potencies of sulphonylureas in long term usage.…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between the Pharmacokinetics and Pharmacodynamic Effects of Oral Hypoglycaemic Drugs

Ferner

Chaplin

1987

Clinical Pharmacokinetics

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Oral hypoglycaemic drugs have widely differing pharmacokinetic properties. Possible pharmacodynamic benefits include greater efficacy and fewer adverse effects. In general, it has not been possible to demonstrate unequivocal differences in clinical efficacy between the sulphonylureas during long term use, although there are clear differences in potency. These differences have been emphasised to the extent that the term 'second-generation' has been used for the most potent sulphonylureas, but there is little to suggest that potency is of any therapeutic significance. Trials to study differences in efficacy have rarely been of acceptable design. They have often used fixed doses of drugs, begging the question of whether true potency ratios have been established for chronic treatment. They have rarely involved substantial numbers of patients in double-blind crossover studies with a suitable washout period. Trials which show that there is a clear relationship between drug concentrations in blood and drug effects (whether therapeutic effects or adverse effects such as severe hypoglycaemia) are generally lacking. Qualitative and semiquantitative analysis of adverse effects supports the concept that drugs with a long half-life (e.g. chlorpropamide), renally excreted active metabolites (e.g. acetohexamide) or unusual properties (e.g. glibenclamide, which accumulates progressively in islet tissue) are more likely to cause prolonged hypoglycaemia, which may be fatal. The major adverse effect of treatment with biguanides is lactic acidosis, and this probably occurs more commonly in patients treated with phenformin than those treated with metformin because of pharmacogenetic variation in phenformin metabolism. The available evidence therefore favours the use of drugs with a short elimination half-life which are extensively metabolised and which have no active metabolites.

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Antidiabetic Drugs After the University Group Diabetes Program (UGDP)

Cited by 21 publications

References 0 publications

Metformin-associated lactic acidosis in Sweden 1977–1991

Metformin-associated lactic acidosis in Sweden 1977–1991

Role of metformin in treatment of diabetes mellitus

The Relationship Between the Pharmacokinetics and Pharmacodynamic Effects of Oral Hypoglycaemic Drugs

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